Biomedical ultrasound, at frequencies of approximately 1-2 MHz and intensities of approximately 1-30 W/cm2 causes a number of non-thermal biological effects in plant roots, cultured single and multicell (spheroids) systems, and animal tissues. These effects include decreased growth, cell cycle perturbations, perturbations in macromolecular syntheses, and induction of chromosomal anomalies in plant root and animal tissues; and lysis, loss of viability, decreased growth rate, and increased giant cell formation in cultured mammalian cells. The proposal's objective is to expand our understanding of the biological and biophysical basis for the induction of perturbations in organized multicellular biological systems. In vivo experiments with Chinese hamster cheek pouch epithelial cells and tissue cultures will assess for cell proliferation, chromosomal ("classical" and nonclassical) anomalies, and chromosomal banding patterns. In vitro studies with multicell spheroids will assess for ultrasonically-induced biological effects (lysis, cell progression, viability, macromolecular syntheses (DNA, RNA, protein), chromosomal anomalies) under a variety of environmental conditions and exposure modes (continuous wave vs. pulsed, increased atmospheric pressure) permitting, inhibiting or enhancing acoustic cavitation. A model is proposed to explain enhanced acoustic cavitation with pulsed ultrasound: with appropriate combinations of intensity, pulse length and duty cycle bubbles of a size appropriate for ultrasonically-induced explosive growth are produced. The results obtained should be directly relevant to assessments of the safety of diagnostic and therapeutic applications of ultrasound and should give an indication of the extent to which extrapolation to mammalian in vivo systems is possible from the existing body of knowledge concerning ultrasound effects on plants, cultured mammalian cells, mammalian tissues, and in vitro multicell mammalian systems.